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Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings
In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024679/ https://www.ncbi.nlm.nih.gov/pubmed/35457051 http://dx.doi.org/10.3390/ijms23084230 |
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author | Alvarez-Mora, Maria Isabel Blanco-Palmero, Victor Antonio Quesada-Espinosa, Juan Francisco Arteche-Lopez, Ana Rosa Llamas-Velasco, Sara Palma Milla, Carmen Lezana Rosales, Jose Miguel Gomez-Manjon, Irene Hernandez-Lain, Aurelio Jimenez Almonacid, Justino Gil-Fournier, Belén Ramiro-León, Soraya González-Sánchez, Marta Herrero-San Martín, Alejandro Octavio Pérez-Martínez, David Andrés Gómez-Tortosa, Estrella Carro, Eva Bartolomé, Fernando Gomez-Rodriguez, Maria Jose Sanchez-Calvin, María Teresa Villarejo-Galende, Alberto Moreno-Garcia, Marta |
author_facet | Alvarez-Mora, Maria Isabel Blanco-Palmero, Victor Antonio Quesada-Espinosa, Juan Francisco Arteche-Lopez, Ana Rosa Llamas-Velasco, Sara Palma Milla, Carmen Lezana Rosales, Jose Miguel Gomez-Manjon, Irene Hernandez-Lain, Aurelio Jimenez Almonacid, Justino Gil-Fournier, Belén Ramiro-León, Soraya González-Sánchez, Marta Herrero-San Martín, Alejandro Octavio Pérez-Martínez, David Andrés Gómez-Tortosa, Estrella Carro, Eva Bartolomé, Fernando Gomez-Rodriguez, Maria Jose Sanchez-Calvin, María Teresa Villarejo-Galende, Alberto Moreno-Garcia, Marta |
author_sort | Alvarez-Mora, Maria Isabel |
collection | PubMed |
description | In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene. |
format | Online Article Text |
id | pubmed-9024679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90246792022-04-23 Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings Alvarez-Mora, Maria Isabel Blanco-Palmero, Victor Antonio Quesada-Espinosa, Juan Francisco Arteche-Lopez, Ana Rosa Llamas-Velasco, Sara Palma Milla, Carmen Lezana Rosales, Jose Miguel Gomez-Manjon, Irene Hernandez-Lain, Aurelio Jimenez Almonacid, Justino Gil-Fournier, Belén Ramiro-León, Soraya González-Sánchez, Marta Herrero-San Martín, Alejandro Octavio Pérez-Martínez, David Andrés Gómez-Tortosa, Estrella Carro, Eva Bartolomé, Fernando Gomez-Rodriguez, Maria Jose Sanchez-Calvin, María Teresa Villarejo-Galende, Alberto Moreno-Garcia, Marta Int J Mol Sci Case Report In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene. MDPI 2022-04-11 /pmc/articles/PMC9024679/ /pubmed/35457051 http://dx.doi.org/10.3390/ijms23084230 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Case Report Alvarez-Mora, Maria Isabel Blanco-Palmero, Victor Antonio Quesada-Espinosa, Juan Francisco Arteche-Lopez, Ana Rosa Llamas-Velasco, Sara Palma Milla, Carmen Lezana Rosales, Jose Miguel Gomez-Manjon, Irene Hernandez-Lain, Aurelio Jimenez Almonacid, Justino Gil-Fournier, Belén Ramiro-León, Soraya González-Sánchez, Marta Herrero-San Martín, Alejandro Octavio Pérez-Martínez, David Andrés Gómez-Tortosa, Estrella Carro, Eva Bartolomé, Fernando Gomez-Rodriguez, Maria Jose Sanchez-Calvin, María Teresa Villarejo-Galende, Alberto Moreno-Garcia, Marta Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings |
title | Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings |
title_full | Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings |
title_fullStr | Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings |
title_full_unstemmed | Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings |
title_short | Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings |
title_sort | heterozygous and homozygous variants in sorl1 gene in alzheimer’s disease patients: clinical, neuroimaging and neuropathological findings |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024679/ https://www.ncbi.nlm.nih.gov/pubmed/35457051 http://dx.doi.org/10.3390/ijms23084230 |
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